Our long-term goal for this project is to study the molecular mechanisms that govern proper kidney development in the embryonic mouse. A mouse strain harboring a targeted disruption of the winged-helix transcription factor Brain Factor-2 (BF-2) has revealed a vital role for this gene in kidney development. Our present working hypothesis is that BF-2 regulates the expression of a secreted factor from renal stromal cells that is required for epithelialization of the surrounding nephrogenic progenitor cells, while also regulating the proliferation and differentiation of the stromal population. In order to study these hypotheses, three lines of investigation are planned: 1) analyzing differential gene expression of renal stroma from BF +/+ and BF-2 -/- embryos in order to identify novel genes involved in kidney morphogenesis, 2) in vitro organ culture experiments in which kidney rudiments are co-cultured with stroma isolated from BF-2 +/- and BF-2 -/- embryos in order to examine directly what role stroma has on the epithelialization of early kidney structures, and 3) we will test the rate of proliferation and the stage of differentiation of renal stroma in WT and BF-2 -/- kidneys by examining the expression of molecular markers of the cell cycle and differentiation.